Studies have been undertaken to elucidate the structures of various lens proteins from human lens and from an animal model of cataract called the Philly mouse. In each case marked changes in protein composition occur during cataract development. In addition there are known to be numerous structural modifications to human crystallins which occur during lens aging and cataractogenesis. We have been able to produce a number of these modifications to crystallins including crosslinking of polypeptides, formation of blue fluorophores, pigmentation and formation of heavy molecular weight aggregates, in vitro by using a photosensitized oxidation system. These effects were shown to be mediated by singlet molecular oxygen, a highly reactive excited state of oxygen, produced by the interaction of light and a photosensitizer. We have demonstrated that compounds endogenous to the human lens can act as photosensitizers. These compounds absorb near UV light at wavelengths greater than 330 nm. Light of these wavelengths is abundant in the lens. The photosensitizers appear to be bound to the crystallins, especially the insoluble protein, and accumulate with age. We believe that photosensitized oxidation mediated by singlet oxygen could be playing a major role in vivo in human lens aging and cataractogenesis.